Adeno-associated virus (AAV) is a dependent parvovirus. That is, it requires coinfection with another virus (either adenovirus or certain members of the herpes virus group) in order to undergo a productive infection in cultured cells. In the absence of coinfection with helper virus, the AAV genome integrates via its ends into the host genome in a site specific manner and resides there in a latent state until the cell is infected with helper virus. Then the AAV DNA is "rescued", replicates and establishes a normal productive infection. AAV has a broad host range for infectivity, it is ubiquitous in humans, it can be concentrated to titers exceeding 109 infectious units per milliliter, and is a completely nonpathogenic integrating viruses. The availability of a infectious recombinant AAV clone, helper-free packaging system, and site-specific integration have provided us with a manipulable system which has tremendous potential as a eucaryotic viral vector. The overall objective of the proposed work is to fully test the feasibility of AAV as a cell type transducing viral vector. The immediate specific aims of the proposed research are as follows: 1. To characterize AAV as a vector in some key specific cell types in culture. 2. To test the feasibility of using AAV hybrid virions for the introduction and expression of genes in the animal. 3. To test animal model systems for specific delivery and correction of well characterized genetic defects.